A large part of the medial temporal lobe consists of the hippocampal formations. Neuropathologic and clinical studies place atrophy in the hippocampal formations central in the processes related to the development of Alzheimer's disease (AD). Neuropathologic studies show that the hippocampal formations are among the first to be diseased by the two classic lesions in AD, neuritic plaques and tangles. The hippocampal formations are also involved in short and long term memory, disturbances in which are one of the sentinel cognitive signs of AD. Hippocampus formations have also been shown to be smaller in persons with AD compared to controls. This evidence has led to the proposal that hippocampal atrophy be used as an aid to the diagnosis of AD and a predictor of future AD. Because there is evidence from several different types of studies that the hippocampus plays a central role in the AD, examining risk factors for hippocampal atrophy may help to gain insight into the etiology of AD. As a putative intermediate step in the dementing process, research on risk factors for hippocampal atrophy may help to formulate possible interventions in the early stages of AD. To date studies of risk factors for hippocampal atrophy are limited to small studies of socio-economic correlates. This proposed study makes use of data from the Rotterdam Scan Study (RSS). NIA supports the measurement of the hippocampal volume on data already collected as a part of the RSS. Participants are aged 60-90 years and at risk for developing dementia. They were randomly selected within age and sex strata from the on-going Rotterdam Study, which was started in 1990. As a part of the Rotterdam Study a wide range of risk factors have been collected, giving us the opportunity to examine established as well as new factors hypothesised to influence the risk for AD, including cardiovascular risk factors. Progress. Post processing of the MRI images obtained with 3D HASTE sequences began in November 1998. Multi-planar reconstruction is performed on a MRI console. Coronal slices are reconstructed perpendicular to the body of the hippocampus; slices are 1.5 mm thick with no gap. Data are transported to a MAGICView workstation, where regions of interest (ROI) are contoured with a mouse-driven cursor. The subiculum, dentate gyrus and CA1-CA4 included in the ROI of the hippocampus. Measurements of the amygdala are also made. All volumes are measured separately for the right and left side. One rater is performing the readings. The whole procedure takes 45 minutes per subject. Three hundred scans have been read. Based on 12 scans re-read within 2 months, the intra-rater reliability (measured by the intra-class correlation coefficient) was as follows: left hippocampus: 0.93; right hippocampus, 0.90; left amygdala, 0.82; right amygdala, 0.78.In September, volumetric reading of the hippocampus began on the 575 scans available on the HAAS cohort. The right and left hippocampal volumes are estimated by contouring ROI with a mouse-driven cursor using similar landmarks as the Rotterdam Study. This is done on coronal scans reconstructed perpendicular to the body of the hippocampus. The post-processing is done with Med-Ex software. In addition, the total intracranial volume is estimated to correct the hippocampus volume for head size.